08/2025 journal articles
EDITORIAL: BRAIN-PENETRANT ANTIBODIES FOR ALZHEIMER’S DISEASE: THE NEXT GENERATION?
C.H. van Dyck
J Prev Alz Dis 2025;8(12)
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CITATION:
C.H. van Dyck (2025): Editorial: Brain-penetrant antibodies for Alzheimer’s disease: The next generation?. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100314
EDITORIAL : TARGETING TAU FOR ALZHEIMERS DISEASE THROUGH OGA INHIBITION
Michael S. Rafii
J Prev Alz Dis 2025;8(12)
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CITATION:
Michael S. Rafii (2025): Editorial: Targeting tau for Alzheimers disease through OGA inhibition. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100309
EDITORIAL: GENE AND GENETIC THERAPIES IN ALZHEIMER’S DISEASE AND OTHER DEMENTIAS
Robert C. Alexander
J Prev Alz Dis 2025;8(12)
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CITATION:
Robert C. Alexander (2025): Editorial: Gene and genetic therapies in Alzheimer’s disease and other dementias. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100313
EDITORIAL : STRUCTURAL EQUATION MODELING CONFIRMS INTERACTION OF ALZHEIMER’S DISEASE AND VASCULAR DISEASE IN HIPPOCAMPAL INJURY
Gary A. Rosenberg
J Prev Alz Dis 2025;8(12)
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CITATION:
Gary A. Rosenberg (2025): Editorial: Structural equation modeling confirms interaction of Alzheimer’s disease and vascular disease in hippocampal injury. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100255
BISPECIFIC BRAIN-PENETRANT ANTIBODIES FOR TREATMENT OF ALZHEIMER’S DISEASE
Dag Sehlin, Greta Hultqvist, Wojciech Michno, Ximena Aguilar, Amelia D Dahlén, Enrica Cerilli, Nadja M Bucher, Sara Lopes van den Broek, Stina Syvänen
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryThe emerging class of bispecific antibodies represents a significant advancement in Alzheimer’s disease (AD) immunotherapy by addressing the limited brain concentrations achieved with conventional monoclonal antibodies. The majority of bispecific antibodies developed for AD treatment utilize transferrin receptor (TfR1)-mediated transcytosis to enhance blood-brain barrier (BBB) penetration, resulting in higher and more uniform brain concentrations compared to conventional antibodies. This improved delivery has demonstrated superior efficacy in reducing brain amyloid-beta (Aβ) burden. Additionally, TfR1-mediated delivery may help mitigate adverse effects such as amyloid-related imaging abnormalities (ARIA). This is likely achieved by a reduction in antibody accumulation at vascular Aβ deposits, resulting from the combined effects of lower dosing and a different brain entry route when using bispecific antibodies. Besides targeting Aβ, bispecific antibodies have been engineered to address other key pathological features of AD, including tau pathology and neuroinflammatory targets, which are critical drivers of disease progression. These antibodies also show promise in diagnostic applications, particularly as radioligands for antibody-based positron emission tomography (immunoPET), leveraging their rapid brain delivery and efficient and specific target engagement. Moreover, the principles of bispecific antibody technology have been adapted for use beyond immunotherapy. The incorporation of TfR1-binding domains into enzymes, antisense oligonucleotides, or viral vectors such as adeno-associated viruses broadens their therapeutic potential. These approaches may enable more efficient treatment strategies, not only for AD but also for other neurological disorders, by facilitating the delivery of diverse therapeutic agents across the BBB.
CITATION:
Dag Sehlin ; Greta Hultqvist ; Wojciech Michno ; Ximena Aguilar ; Amelia D Dahlén ; Enrica Cerilli ; Nadja M Bucher ; Sara Lopes van den Broek ; Stina Syvänen (2025): Bispecific brain-penetrant antibodies for treatment of Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2025.8
RESULTS OF THE FIRST-IN-HUMAN, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-ASCENDING DOSE STUDY OF BIIB113 IN HEALTHY VOLUNTEERS
Flavia C. Nery, Maciej Kaliszczak, Ben Suttle, Lori Jones, Shuang Wu, Jing Xie, Gioacchino Curiale, Esin Yesilalan, Beth Hirschhorn, Denisa Wilkes, Dave Singh, Martin Bolin, Sangram Nag, Andrea Varrone, Per Stenkrona, Anton Forsberg Morén, Christer Halldin, Jeffrey Yachnin, H. Moore Arnold, Szofia Bullain, Jaren Landen, Diana Gallagher, Heike Hering
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Preclinical studies have demonstrated that inhibition of the O-linked β-N-acetylglucosaminidase enzyme increases tau O-linked β-N-acetylglucosaminylation and may attenuate tau pathology in Alzheimer’s disease.
OBJECTIVES: To examine the safety, tolerability, pharmacokinetics, and target occupancy of single- and multiple-ascending oral doses of the small-molecule O-linked β-N-acetylglucosaminidase inhibitor, BIIB113.
DESIGN: Study 276HV101 was a first-in-human, multicenter, Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose trial.
SETTING: 72 participants were enrolled from February 2022 through July 2023.
PARTICIPANTS: Adult healthy female and infertile/vasectomized male participants.
INTERVENTION: In the single-ascending dose substudy, participants received a single dose of placebo or BIIB113 0.5, 3, 15, or 50 mg. In the 14-day multiple-ascending dose substudy, participants received placebo or BIIB113 15 or 50 mg once daily. In the target occupancy substudy, participants received either a single dose of BIIB113 0.5 or 3 mg or a once-daily dose of BIIB113 0.5 mg.
MEASUREMENTS: Safety and tolerability were measured by incidence of adverse events. Pharmacokinetic and concentration-time profiles were assessed. Target occupancy was evaluated using the carbon-11 BIO-1819,578 radioligand.
RESULTS: BIIB113 was generally well tolerated. Pharmacokinetics were linear over the dose range, with a half-life of approximately 30 h. Administration with food decreased the rate but did not affect the extent of absorption. There were no clinically meaningful differences in pharmacokinetics between elderly and nonelderly participants. Multiple once-daily doses of BIIB113 0.5 mg maintained a target occupancy of ≥90 % up to 48 h.
CONCLUSIONS: BIIB113 was well tolerated and achieved high levels of target occupancy.
CITATION:
Flavia C. Nery ; Maciej Kaliszczak ; Ben Suttle ; Lori Jones ; Shuang Wu ; Jing Xie ; Gioacchino Curiale ; Esin Yesilalan ; Beth Hirschhorn ; Denisa Wilkes ; Dave Singh ; Martin Bolin ; Sangram Nag ; Andrea Varrone ; Per Stenkrona ; Anton Forsberg Morén ; Christer Halldin ; Jeffrey Yachnin ; H. Moore Arnold ; Szofia Bullain ; Jaren Landen ; Diana Gallagher ; Heike Hering (2025): Results of the first-in-human, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study of BIIB113 in healthy volunteers. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100302
CTAD TASKFORCE: GENETIC THERAPIES IN ALZHEIMER’S DISEASE
D. Jakabek, A.M. Isaacs, B. De Strooper, M. Tuszynski, R. Lane, O. Uspenskaya, E. McDade, M.S. Rafii, C.J. Mummery
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryThere are an increasing number of genetic approaches to treating Alzheimer’s disease and other dementias, with some promising results from early-phase trials. This prompted the convention of the first EU-US CTAD Task Force on genetic therapies in Alzheimer’s disease in October 2024. Preclinical studies and clinical trials of genetic therapies in Alzheimer’s disease and other dementias are presented here with key lessons for the field. Importantly, there are several challenges and opportunities unique to neurogenetic therapies which were reviewed and discussed, including means of genetic manipulation, adverse events, monitoring, timing of therapy, and the importance of patient involvement in trial design. Continued collaboration across disciplines will accelerate development of neurogenetic therapeutics.
CITATION:
D. Jakabek ; A.M. Isaacs ; B. De Strooper ; M. Tuszynski ; R. Lane ; O. Uspenskaya ; E. McDade ; M.S. Rafii ; C.J. Mummery (2025): CTAD taskforce: genetic therapies in Alzheimer’s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100269
CEREBROVASCULAR DISEASE IN ALZHEIMER\'S DISEASE: BRAIN STRUCTURE AS A CRITICAL MEDIATOR OF COGNITIVE DECLINE
Chao Tang, Yaqi Ding, Jiaxin Yang, Dian He
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: The co-occurrence of Alzheimer's disease and cerebrovascular disease is increasingly prevalent in aging populations, yet the mechanisms of their interaction remain incompletely understood. This study aims to investigate the associations between CVD and AD and their composite effects on cognitive function, identifying key mediating pathways in these relationships.
METHODS: Participants underwent standardized clinical evaluations, detailed neuropsychological testing, and comprehensive neuropathological examinations. Structural equation modeling with multiple mediation analyses was employed to disentangle direct and indirect effects of vascular pathology on cognition and identify key mediating pathways. Relationships between specific cognitive domain assessments and whole brain and hippocampal volumes were analyzed, while interactions between traditional AD biomarkers (amyloid, tau) and vascular factors were examined.
RESULTS: CVD substantially increased AD risk. Structural equation modeling revealed that vascular factors influence cognitive performance primarily through hippocampal atrophy, APOE genotype, and cerebral atrophy. Participants with concomitant AD +CVD pathology displayed a distinctive hybrid pattern of brain-cognition relationships, with stronger correlations between hippocampal atrophy and cognitive performance compared to pure AD or CVD cases. Pathway-specific analysis demonstrated that hippocampal atrophy served as the strongest mediator of vascular effects on cognition, followed by cerebral atrophy and APOE genotype.
CONCLUSION: Our findings demonstrate that cerebrovascular disease significantly increases the risk of Alzheimer's disease and substantially influences its clinical expression through multiple pathways, with structural brain changes serving as critical mediators of vascular effects on cognition. These results highlight the importance of addressing vascular health as an integral component of strategies to prevent and treat Alzheimer's disease and related cognitive disorders.
CITATION:
Chao Tang ; Yaqi Ding ; Jiaxin Yang ; Dian He (2025): Cerebrovascular disease in Alzheimer's disease: Brain structure as a critical mediator of cognitive decline. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100209
THE EFFECT OF MODIFIED DONANEMAB TITRATION ON AMYLOID-RELATED IMAGING ABNORMALITIES WITH EDEMA/EFFUSIONS AND AMYLOID REDUCTION: 18-MONTH RESULTS FROM TRAILBLAZER-ALZ 6
Hong Wang, Emel Serap Monkul Nery, Paul Ardayfio, Rashna Khanna, Diana Otero Svaldi, Sergey Shcherbinin, Wen Xu, Scott W. Andersen, Paula M. Hauck, Dawn A. Brooks, Emily C. Collins, Stephen Salloway, Mark A. Mintun, John R. Sims
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryThe TRAILBLAZER-ALZ 6 study (NCT05738486) evaluated the effect of different donanemab dosing regimens on amyloid-related imaging abnormalities with edema/sulcal effusions (ARIA-E). The modified titration arm met the primary outcome and significantly reduced ARIA-E frequency compared with the standard dosing while maintaining a similar pharmacodynamic effect on amyloid reduction at 24 weeks. Primary outcome and 52-week data were previously published. Completed study results at 76 weeks are reported here. ARIA-E frequencies were 15.6 % and 24.2 % in the modified titration and standard arms, respectively. ARIA-E radiographic severity was significantly lower (p = 0.015) with modified titration than with standard dosing. Additionally, symptomatic ARIA-E frequency was lower with modified titration versus standard dosing (2.8 % vs 4.8 %). The frequency of serious adverse events was comparable between the modified titration and standard dosing arms. A more gradual titration of donanemab dosing significantly reduced ARIA-E risk versus standard dosing.
CITATION:
Hong Wang ; Emel Serap Monkul Nery ; Paul Ardayfio ; Rashna Khanna ; Diana Otero Svaldi ; Sergey Shcherbinin ; Wen Xu ; Scott W. Andersen ; Paula M. Hauck ; Dawn A. Brooks ; Emily C. Collins ; Stephen Salloway ; Mark A. Mintun ; John R. Sims (2025): The effect of modified donanemab titration on amyloid-related imaging abnormalities with edema/effusions and amyloid reduction: 18-month results from TRAILBLAZER-ALZ 6. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100266
THE ALZHEIMER’S DISEASE COOPERATIVE STUDY – ACTIVITIES OF DAILY LIVING DEPENDENCE SCORE: REVISION AND VALIDATION OF AN ALGORITHM EVALUATING PATIENT DEPENDENCE ACROSS THE SPECTRUM OF AD SEVERITY
Julie M. Chandler, Claire J. Lansdall, Wenyu Ye, Fiona McDougall, Mark Belger, Balazs Toth, Xiaojuan Mi, Kaycee M. Sink, Alexandra S. Atkins
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Increasing dependence on informal and formal caregivers in Alzheimer’s disease (AD) contributes to high societal cost. Treatments that delay time to increased dependence/care needs would be clinically meaningful, but these outcomes are rarely collected in early AD clinical trials. The 2015 ADCS-ADL dependence algorithm was created to estimate level of dependence in AD.
OBJECTIVES: To revise the original dependence algorithm to improve accuracy of dependence scores (DS) across AD severity, including early symptomatic AD.
DESIGN: Secondary data analysis.
SETTING: Community cohort; randomized clinical trial.
PARTICIPANTS: 14,000 participants enrolled across GERAS-EU observational study and 12 AD clinical trials.
MEASUREMENTS: Three-phase algorithm revision: 1) reassess ADCS-ADL items to identify those appropriate for assessing dependence; 2) (a) assign individual item responses to degrees of assistance and (b) to operationalize assignment of DS based on extent of total assistance needed; and 3) validate revised algorithm in multiple datasets across AD severity from mild cognitive impairment due to AD to moderate-severe AD.
RESULTS: The revised DS (0-6) algorithm classified most participants with early symptomatic AD as independent or moderately independent (DS<3) at baseline. With disease progression over time, the proportion of participants who were mildly to fully dependent (DS≥3) increased across AD severity. Increased DS was associated with incremental worsening of clinical outcomes.
CONCLUSIONS: The revised ADCS-ADL DS algorithm provides a supplementary approach to evaluate the impact of emerging treatments on independence/care needs in AD and may be useful in clinical trials where the ADCS-ADL has been collected.
CITATION:
Julie M. Chandler ; Claire J. Lansdall ; Wenyu Ye ; Fiona McDougall ; Mark Belger ; Balazs Toth ; Xiaojuan Mi ; Kaycee M. Sink ; Alexandra S. Atkins (2025): The Alzheimer’s Disease Cooperative Study – Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100261
BRIDGING THE GAP: A CONVERSION FRAMEWORK FOR CDR-SB AND MOCA SCORES IN ALZHEIMER\'S DISEASE AND RELATED DEMENTIA
Babak Haji, Quanwu Zhang, Amir Abbas Tahami Monfared
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Accurate assessment of cognitive impairment is essential to effective Alzheimer’s disease (AD) management and research. However, the absence of validated methods to translate scores between widely used instruments—such as the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) in trials and the Montreal Cognitive Assessment (MoCA) in clinical practice—poses a significant barrier. This limits data harmonization, impedes cross-study comparability, and complicates the integration of clinical and research evidence. Bridging this gap is critical for consistent staging, longitudinal monitoring, and data-driven decision-making in AD and related dementias.
OBJECTIVES: To develop and validate bidirectional score conversion tables between CDR-SB and MoCA using a large, diverse cohort spanning the full spectrum of cognitive function.
DESIGN: Retrospective, cross-sectional analysis using equipercentile equating with log-linear smoothing. Optimal smoothing parameters were selected by minimizing mean squared error, Akaike Information Criterion, and Bayesian Information Criterion. Concordance was assessed using Spearman’s rank correlation and Bland-Altman plots.
SETTING: National Alzheimer’s Coordinating Center (NACC), aggregating standardized assessments from 35 U.S.-based Alzheimer’s Disease Research Centers.
PARTICIPANTS: 23,717 individuals (59,871 visits) with same-day CDR-SB and MoCA assessments from January 2015 to September 2024, spanning normal cognition, mild cognitive impairment (MCI), and dementia.
INERVENTION: None; this was a secondary analysis of existing data.
MEASUREMENTS: Primary measures included CDR-SB (0–18; higher = greater impairment) and MoCA (0–30; higher = better cognition). Bidirectional crosswalk tables were derived using equipercentile equating.
RESULTS: CDR-SB and MoCA scores showed strong inverse correlation (Spearman’s ρ = –0.68; p < 0.001). Crosswalk tables demonstrated good agreement across the cognitive spectrum and performed consistently in the full cohort and an AD-specific subgroup.
CONCLUSIONS: This study provides the first validated, bidirectional CDR-SB–MoCA crosswalk, supporting data harmonization and consistent interpretation of cognitive severity across research and clinical settings.
CITATION:
Babak Haji ; Quanwu Zhang ; Amir Abbas Tahami Monfared (2025): Bridging the gap: A conversion framework for CDR-SB and MoCA scores in Alzheimer's disease and related dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2025.8
NEW-GENERATION ANTIDIABETIC MEDICATIONS AND DEMENTIA RISK IN OLDER ADULTS WITH TYPE 2 DIABETES: A RETROSPECTIVE COHORT STUDY
Avi Cohen, Stephen Z Levine, Gabriel Vainstein, Michal Schnaider Beeri, Galit Weinstein
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: New-generation antidiabetic medications may have therapeutic potential for dementia, beyond their glycemic effects. However, information from observational studies exploring the association between new-generation antidiabetic use and dementia risk is limited.
OBJECTIVES: To examine the association between new-generation antidiabetic medication use and dementia risk.
DESIGN: Retrospective cohort study using electronic health records of a large non-profit health maintenance organization.
PARTICIPANTS: 84,798 dementia-free individuals aged ≥65y with type 2 diabetes.
MEASUREMENTS: Antidiabetic medication exposure was based on purchased prescriptions and was used as a time-varying variable. Exposure periods were defined as periods in which either dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or glucagon-like peptide-1 analogs (GLP-1a) or their combinations were used, otherwise unexposed. Dementia classification was based on the International Classification of Diseases, Ninth Revision codes or antidementia medication prescriptions. Cox regression models were fitted to quantify the association between antidiabetic medication use and incident dementia. Models were adjusted for 13 potential sources of confounding using inverse-probability weighting.
RESULTS: Among 84,798 individuals with a mean diabetes onset age of 66.4 ± 7.5 years, the median follow-up for dementia risk was 8.7 years (Q1-Q3: 5.4–12.8). Dementia was diagnosed in 11,642 (13.7%) individuals. New-generation medication use was associated with reduced dementia risk (HR = 0.69; 95% CI, 0.66–0.73) and by drug classes (DPP-4i, HR 0.67 [95% CI 0.63–0.71]; SGLT-2i, 0.63 [95% CI 0.56–0.70], GLP-1a, 0.61 [95% CI 0.54–0.69].
CONCLUSION: The results of this large-scale study suggest that new-generation antidiabetic medication use may be associated with lower dementia risk in older adults with T2D.
CITATION:
Avi Cohen ; Stephen Z Levine ; Gabriel Vainstein ; Michal Schnaider Beeri ; Galit Weinstein (2025): New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100199
A MODELLING APPROACH TO DERIVE POPULATION-SPECIFIC CUTOFF FOR PLASMA P-TAU217
Tau Ming Liew, Alzheimer\'s Disease Neuroimaging Initiative
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryPlasma pTau-217 shows promise for detecting Alzheimer’s disease, but needs population-specific cutoffs for effective use. Conventional cutoff determination relies on invasive or costly gold-standards, limiting scalability. This study evaluated Finite Mixture Modelling (FMM) for establishing cutoffs without gold-standards. FMM was applied to derive cutoffs for Lumipulse plasma p-Tau217 and p-Tau217/Aβ42 ratio among 1039 ADNI participants, with validation conducted in a subset with amyloid PET data (n = 711). Additionally, simulations were conducted to determine the minimum sample size for reliable FMM estimation. The results showed that FMM-derived cutoffs effectively classified participants into brain amyloid-negative, -positive, and -indeterminate groups, with an indeterminate proportion <20 %, negative and positive predictive values near or above 90 %, and with p-Tau217/Aβ42 outperforming p-Tau217. These FMM-derived cutoffs demonstrated test performance that surpassed several previously-established cutoffs, including the recent FDA-approved cutoff. At least 900 samples were needed for reliable cutoff estimation. In conclusion, this study demonstrated the effectiveness of a modelling approach for estimating plasma p-Tau217 cutoffs without reliance on gold-standards. This approach simplifies the determinating of population-specific cutoffs and facilitates adoption of plasma p-Tau217 in communities lacking access to gold-standards, including some LMICs.
CITATION:
Tau Ming Liew ; Alzheimer's Disease Neuroimaging Initiative (2025): A modelling approach to derive population-specific cutoff for plasma p-Tau217. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100264
IMPACT OF CARDIOVASCULAR RISK FACTORS ON PLASMA BIOMARKERS IN PREDICTION OF ALZHEIMER\'S AND CEREBROVASCULAR NEUROPATHOLOGY
Camilo Bermudez, Jeremy A. Syrjanen, Nikki H. Stricker, Alicia Algeciras-Schimnich, Naomi Kouri, Walter K. Kremers, Ronald C. Petersen, Clifford R. Jack Jr, David S. Knopman, Dennis W. Dickson, Darren M. Rothberg, Christina M. Moloney, Baayla D.C. Boon, Aivi T. Nguyen, R. Ross Reichard, Melissa E. Murray, Michelle M. Mielke, Prashanthi Vemuri, Jonathan Graff-Radford
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Plasma biomarkers for Alzheimer’s disease and neurodegeneration have shown accurate prediction of underlying neuropathology. However, chronic cardiovascular risk factors such as diabetes and hypertension are associated with plasma biomarker levels and can influence the accurate prediction of underlying neuropathologic changes.
OBJECTIVE: To understand the interaction between plasma biomarkers of Alzheimer’s disease and neurodegeneration with cardiovascular risk factors in relation to neuropathologic change in a heterogenous population to ascertain a more accurate utilization of these biomarkers.
DESIGN: Retrospective, case-control study.
SETTING: Population-based, Olmstead county, Minnesota, USA.
PARTICIPANTS: Three-hundred and fifty-one participants (aged 87.4 ± 7.5 years) with brain autopsy and antemortem plasma biomarker testing.
MEASUREMENTS: Plasma biomarker testing for Aβ42/40, p-tau181, GFAP, and NfL using Quanterix Simoa assays. Cardiovascular risk factors were quantified by a composite score of cardiovascular metabolic conditions (CMC) consisting of a binary history of diabetes, congestive heart failure, stroke, coronary artery disease, atrial fibrillation, hypertension, or dyslipidemia. Plasma biomarkers and cardiovascular metabolic conditions score were Z-scored and neuropathologic scales were binarized into high and low categories. Outcomes included elevated microvascular (Kalaria) and macrovascular (Strozyk) neuropathologic scales as well as Alzheimer’s disease neuropathologic change (ADNC), Thal phase, Braak stage, and neuritic plaque score. Multivariate logistic regression models incorporated interaction terms between plasma biomarkers and CMC while controlling for age, sex, cognitive impairment, and BMI.
RESULTS: We observed that at higher cardiovascular metabolic conditions score, the association between GFAP and overall ADNC (OR = 0.61 [0.42, 0.89]), Thal phase (OR = 0.48 [0.33, 0.71]), and Braak Stage (OR = 0.56 [0.37, 0.84]), became weaker, while the association with Strozyk score (OR = 1.65 [1.11, 2.46]) was stronger with higher CMC. Meanwhile, at higher CMC Aβ42/40 became more strongly negative with high Braak stage (OR = 0.63 [0.47, 0.85]), neuritic plaque score (OR 0.70 [0.52, 0.95]), Kalaria score (OR = 0.71 [0.57, 0.88]), and Strozyk score (OR = 0.60 [0.43, 0.83]). The association between p-tau181 and Thal phase (OR = 1.43 [1.00, 2.04]) was stronger at higher CMC while the association between p-tau181 and Strozyk score (OR = 0.47 [0.31, 0.71]) was weaker at higher CMC. There was no interaction between NfL and CMC score for any metric of neuropathologic change.
CONCLUSION: Understanding how cardiovascular risk factors can modulate plasma biomarkers is important for their interpretation with respect to underlying pathology and their clinical application in screening, diagnosis, and prognosis of neurodegenerative diseases.
CITATION:
Camilo Bermudez ; Jeremy A. Syrjanen ; Nikki H. Stricker, ; Alicia Algeciras-Schimnich ; Naomi Kouri ; Walter K. Kremers ; Ronald C. Petersen ; Clifford R. Jack Jr ; David S. Knopman ; Dennis W. Dickson ; Darren M. Rothberg ; Christina M. Moloney ; Baayla D.C. Boon ; Aivi T. Nguyen ; R. Ross Reichard ; Melissa E. Murray ; Michelle M. Mielke ; Prashanthi Vemuri ; Jonathan Graff-Radford (2025): Impact of cardiovascular risk factors on plasma biomarkers in prediction of Alzheimer's and cerebrovascular neuropathology. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.1002248
EARLY DETECTION OF ALZHEIMER’S DISEASE USING SMALL RNAS. RESULTS FROM THE EPAD COHORT
Tobias Sikosek, Marco Heuvelman, Jagoda Mika, Mustafa Kahraman, Julia Jehn, Maurice Frank, Alberto Daniel-Moreno, Jessika Ceiler, Jasmin Skottke, Marta Sanchez-Delgado, Patrick Neubert, Christina Rudolf, Kaja Tikk, Rastislav Horos, Jeffrey L. Cummings, Josie Butchart, Craig Ritchie, Jean Manson, Bruno R. Steinkraus, the EPAD consortium
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Alzheimer's disease (AD) is the most common form of dementia, and early diagnosis is crucial to enable effective interventions. Currently, Alzheimer's disease is diagnosed through cognitive assessments, brain imaging and fluid biomarkers focused on determining amyloid (A) and, tau (T) protein levels as well as neurodegeneration (N) in the AT(N) framework. Prognostic biomarkers for predicting cognitive decline within the amyloid positive (Aβ+) individuals would further strengthen the framework.
OBJECTIVES: This study evaluated small RNAs as novel auxiliary biomarkers, independent of the AT(N) framework, either alone or in combination with established protein markers, for detecting the earliest cognitive decline in AD.
DESIGN: The European Prevention of Alzheimer’s Disease (EPAD) clinical trial platform is a prospective, multi-center study designed to investigate biomarkers for preclinical and prodromal AD.
SETTING: Peripheral whole blood RNA sequencing was performed on participants across Europe with no cognitive impairment or very mild cognitive impairment (MCI), stratified by cerebrospinal fluid amyloid levels.
PARTICIPANTS: 1,913 participants, 50 years or older and free of dementia diagnosis at enrollment, were analyzed.
INTERVENTION: (if any) Not applicable.
MEASUREMENTS: Ultra-deep small RNA sequencing was performed on whole blood samples using a refined blocking protocol to eliminate highly abundant erythroid small RNAs, and thereby to open sequencing bandwidth for the discovery of less abundant biomarker RNAs. Biomarker RNAs were deconvolved into plasma or blood cell origin and analyzed for functional relevance. We define high and low amyloid groups based on a cutoff on the p-tau181/Aβ1-42 ratio as determined from cerebrospinal fluid.
RESULTS: We identified a combination of small RNAs that predicted early cognitive decline (Clinical Dementia Rating of 0.5) with an area under the receiver-operator curve of ∼0.7. Notably, when focusing on individuals with cognitive decline and high amyloid burden (Aβ+), the predictive accuracy improved to an AUC of 0.77. This performance could be extended to the entire cohort when combining blood RNA and CSF amyloid markers (AUC 0.76). We conducted bioinformatic analyses to interrogate the likely functional relevance of these small RNAs, uncovering several links to dementia-relevant pathways, including neuronal, cardiovascular, and inflammatory activities. Our findings also suggest that small nucleolar RNAs warrant further investigation as potential disease-relevant markers, in addition to microRNAs.
CONCLUSIONS: Integrating small RNA biomarkers with protein-based assays offers preliminary evidence for stratifying MCI, particularly within the amyloid positive continuum. Small nucleolar RNAs and microRNAs warrant further exploration as complementary diagnostic tools, and their use may enable more precise and effective interventions.
CITATION:
Tobias Sikosek ; Marco Heuvelman ; Jagoda Mika ; Mustafa Kahraman ; Julia Jehn ; Maurice Frank ; Alberto Daniel-Moreno ; Jessika Ceiler ; Jasmin Skottke ; Marta Sanchez-Delgado ; Patrick Neubert ; Christina Rudolf ; Kaja Tikk ; Rastislav Horos ; Jeffrey L. Cummings ; Josie Butchart ; Craig Ritchie ; Jean Manson ; Bruno R. Steinkraus ; the EPAD consortium (2025): Early detection of Alzheimer’s disease using small RNAs. Results from the EPAD cohort. The Journal of Prevention of Alzheimer’s Disease (JPAD).https://doi.org/10.1016/j.tjpad.2025.100257
CAN NON-PHARMACOLOGICAL INTERVENTIONS CHANGE LEVELS OF NEUROFILAMENT LIGHT IN OLDER ADULTS AT RISK OF DEMENTIA? A SECONDARY ANALYSIS OF THE SCD-WELL RANDOMIZED CLINICAL TRIAL
Lehané Masebo, Tim Whitfield, Harriet Demnitz-King, Amanda Heslegrave, Géraldine Poisnel, Antoine Lutz, Eric Frison, Miranka Wirth, Abdul Hye, Frank Jessen, Nicholas J. Ashton, Henrik Zetterberg, Natalie L. Marchant
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Older adults with subjective cognitive decline (SCD) and/or elevated neurofilament light (NfL), a neurodegeneration biomarker, are at increased risk of dementia. Non-pharmacological interventions offer a promising strategy for reducing dementia risk, yet none have utilized NfL as a marker of response in dementia prevention trials.
OBJECTIVE: To investigate the effects of two non-pharmacological interventions on NfL in older adults with SCD.
DESIGN: SCD-Well was an 8-week observer-blinded, randomized, clinical trial with 6-month follow-up, and was a part of the Horizon 2020 European Union-funded "Medit-Ageing" project. Data were analyzed from June 2022 to August 2024.
SETTING: Memory clinics at four sites in France, Germany, Spain, and UK.
PARTICIPANTS: Participants were enrolled from March 2017 to January 2018 after fulfilling SCD research criteria and performing within the normal range on cognitive testing. Of the 147 participants enrolled, 140 were included in this secondary analysis (7 did not consent to venipuncture).
INTERVENTIONS: Participants were randomly allocated to the Caring Mindfulness-Based Approach for Seniors (CMBAS) intervention or a structurally matched Health Self-Management Program (HSMP).
MEASUREMENTS: Plasma NfL was measured at baseline (V1), post-intervention (V2), and 6-month follow-up (V3), using Single molecule array technology, and log-transformed for analyses.
RESULTS: 137 older adults with SCD provided NfL data (mean [SD] age: 72.7 [6.8] years; 62.0 % female; CMBAS, n = 70; HSMP, n = 67). NfL data were available at V1 (n = 136), V2 (n = 119) and V3 (n = 115). The visit-by-arm interaction was not statistically significant, and no significant changes in NfL were observed within the CMBAS or HSMP arms from V1 to V2. However, within the HSMP arm, NfL levels reduced from V1 to V3 (-0.10, 95 % confidence interval [-0.18 to -0.02]). Modified intention-to-treat analyses, which included 140 participants, supported these findings, and additionally recorded significant reductions in the HSMP arm from V1 to V2 (n = 140, -0.07 [-0.14 to -0.00]).
CONCLUSIONS: In this study, NfL levels were reduced at 6-month follow-up after a health self-management program. Future interventions with longer duration, extended follow-up and clinical endpoints will help clarify whether NfL reductions are sustained over extended timeframes and translate to lower dementia incidence.
CITATION:
Lehané Masebo ; Tim Whitfield ; Harriet Demnitz-King ; Amanda Heslegrave ; Géraldine Poisnel ; Antoine Lutz ; Eric Frison ; Miranka Wirth ; Abdul Hye ; Frank Jessen ; Nicholas J. Ashton ; Henrik Zetterberg ; Natalie L. Marchant (2025): Can non-pharmacological interventions change levels of neurofilament light in older adults at risk of dementia? A secondary analysis of the SCD-Well randomized clinical trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100299
THE DIFFERENTIAL EFFECT OF STRENGTH, COGNITIVE AND AEROBIC TRAINING COMBINATIONS ON COGNITIVE PERFORMANCE AND FUNCTIONAL ABILITIES IN ELDERLY WITH COGNITIVE DECLINE: THE FIT4ALZ PROJECT
Ana Filipa Silva, Gilmara Assis, Rui Miguel Silva, Eugenia Murawska-Cia?owicz, Grzegorz Zurek, José Carvalho, Mafalda Sofia Roriz, José Alberto Azevedo, António Sampaio, Telmo Bento, Olivera Jovanovic, Marko Adamovic, Spartaco Grieco, Roberta Germini, Filipe Manuel Clemente
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Despite the global impact of neurodegenerative diseases and ongoing research efforts, pharmacological therapies have shown limited benefits. In contrast, physical exercise, with no side effects, has emerged as a non-pharmacological alternative that can enhance brain structure and function, promoting a healthier neurological phenotype.
OBJECTIVES: This study aimed to explore the effects of aerobic and strength training methods, both with and without cognitive training, on mitigating or reversing cognitive decline in older adults.
DESIGN, SETTING, PARTICIPANTS: In a randomized controlled trial, a total of 350 participants (average age 72.9 ± 6.0 years, 79 % female), with signs of decline (MoCA score below 26), were assigned to one of five groups: i) strength plus cognitive training (STCT, n = 92); ii) strength training (ST, n = 41); iii) aerobic training (AT, n = 97); iv) aerobic plus cognitive training (ATCT, n = 91); v) control (CG, n = 29).
INERVENTION: For 12 weeks, all groups followed a 60 min training session three times a week, tailored to their specific group, with half of the sample adding 20 min of cognitive stimulation after the physical exercise.
MEASUREMENTS: Cognitive and physical assessments were conducted at the start and end of the intervention using the MoCA and the Senior Fitness test. A mixed ANCOVA analysis revealed significant interactions between time and group for all tests.
RESULTS: After the intervention, the CG showed significantly lower scores compared to all experimental groups. The CG also performed significantly worse than the ATCT group (p < 0.001). Additionally, the ATCT outperformed the STCT in the 6-min walk test (p < 0.05), while the STCT showed superior performance in the flexibility tests (sit and reach, back scratch) compared to the CG (p < 0.05).
CONCLUSIONS: Results showed that 12-weeks of aerobic and strength training, with or without cognitive components, improved cognitive performance in older adults with cognitive decline, highlighting the importance of maintaining functional abilities for preserving skills, autonomy, independence, and quality of life in aging.
CITATION:
Ana Filipa Silva ; Gilmara Assis ; Rui Miguel Silva ; Eugenia Murawska-Ciałowicz ; Grzegorz Zurek ; José Carvalho ; Mafalda Sofia Roriz ; José Alberto Azevedo ; António Sampaio ; Telmo Bento ; Olivera Jovanovic ; Marko Adamovic ; Spartaco Grieco ; Roberta Germini ; Filipe Manuel Clemente ; (2025): The differential effect of strength, cognitive and aerobic training combinations on cognitive performance and functional abilities in elderly with cognitive decline: The Fit4Alz project. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100267
ADHERENCE TO AN ANTI-INFLAMMATORY DIET IS ASSOCIATED WITH LOWER ALZHEIMER’S DISEASE MORTALITY: A MODIFIABLE RISK FACTOR IN A NATIONAL COHORT
Ching-Chi Hsu, Shiow-Ing Wang, Sebastian Yu, Eric S. Lin, James Cheng-Chung Wei
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Chronic neuroinflammation contributes to Alzheimer’s disease (AD) pathogenesis, and diet is a modifiable factor influencing inflammation. The impact of an anti-inflammatory diet on AD-specific mortality remains unclear.
OBJECTIVES: To examine the association between adherence to an anti-inflammatory diet (measured as the percentage of dietary energy from anti-inflammatory foods) and AD-specific mortality, as well as all-cause mortality, in a large national cohort, and to determine whether associations differ by sex or race/ethnicity.
METHODS: We analyzed 18,795 U.S. adults (≥18 years) from the 2007–2014 National Health and Nutrition Examination Survey. Anti-inflammatory diet adherence was defined as the percentage of total energy intake from anti-inflammatory foods, categorized as 0 %, <5 %, 5–9.99 %, or ≥10 %. Outcomes were AD-specific mortality and all-cause mortality ascertained via the National Death Index. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality across intake categories, adjusting for demographic, lifestyle, and health factors. Analyses were stratified by sex, race/ethnicity, and age (≥45 years for AD mortality).
RESULTS: Participants with 0 % anti-inflammatory intake had a higher all-cause mortality risk (HR 3.82, 95 % CI 1.18–12.33) compared to those with ≥10 % intake. In the overall analysis, 0 % anti-inflammatory intake showed a trend of reduced AD-specific mortality although its did not reach statistical significance after full adjustment (HR 3.04, 95 % CI 0.74–12.46 vs. ≥10 % intake; p>0.05). Notably, the inverse association between anti-inflammatory diet and AD mortality emerged in subgroup analyses. Male participants and non-Hispanic White participants with 0 % intake had the highest AD mortality hazards (HR 12.83 and 3.77, respectively, vs. ≥10 % intake), indicating significant risk reductions with anti-inflammatory diet in these groups. In contrast, no significant associations were observed in female or non-White subgroups. Even a modest intake of anti-inflammatory foods (≥10 % of calories) was associated with lower AD mortality risk in the above subgroups and with lower all-cause mortality overall.
CONCLUSION: Greater consumption of anti-inflammatory foods was associated with lower all-cause and a trend toward lower AD-specific mortality. The observed protective effects were confined to certain subpopulations (notably men and non-Hispanic Whites). Even a small portion of the diet (10 % of calories) being anti-inflammatory was linked to reduced mortality risk in these groups, suggesting that achievable dietary changes could have an impact. These findings support modifying dietary content is a practical, low-cost intervention that could mitigate neuroinflammation to reduce AD mortality risk.
CITATION:
Ching-Chi Hsu ; Shiow-Ing Wang ; Sebastian Yu ; Eric S. Lin ; James Cheng-Chung Wei (2025): Adherence to an anti-inflammatory diet is associated with lower Alzheimer’s disease mortality: A modifiable risk factor in a national cohort. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100221
TAILORING MULTIDOMAIN INTERVENTION PROGRAMS TO REDUCE COGNITIVE AND PHYSICAL DECLINE IN OLDER ADULTS: EXAMINING RURAL-URBAN DIFFERENCES IN A NATIONWIDE CLUSTER-RANDOMIZED CONTROLLED TRIAL
Min-Yin Ho, Wei-Ju Lee, Ko-Han Yen, Chih-Kuang Liang, Li-Ning Peng, Ming-Hsien Lin, Ching-Hui Loh, Fei-Yuan Hsiao, Liang-Kung Chen
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Frailty and cognitive impairment are major challenges in aging populations. Multidomain interventions targeting physical, cognitive, and nutritional health show promise; however, evidence on rural-urban differences in efficacy remains limited.
OBJECTIVES: To evaluate the impact of rural-urban disparities on the clinical efficacy of a 12-month multidomain intervention for cognitive and physical outcomes in older adults.
DESIGN: Cluster-randomized controlled trial.
SETTING: Community clusters in five cities/counties across Taiwan.
PARTICIPANTS: A total of 1082 adults aged ≥65 years from 40 community clusters were randomized to intervention or control groups.
INTERVENTION: The intervention group received a 12-month program including physical exercise (45 min/session), cognitive training (1 hour/session), and nutritional guidance (15 min/session). The control group received telephone-based health education. This trial was registered at ClinicalTrials.gov (NCT03056768)
MEASUREMENTS: Outcomes included walking speed, grip strength, physical activity (METs), frailty (CHS score), and cognitive function (MoCA), assessed at baseline, 6, and 12 months.
RESULTS: Urban participants showed significantly greater gains in visuospatial/executive function at the 12 month (rural-urban difference 0.63, 95 % CI: 0.26 -1.03), and walking speed at the 12 month (rural-urban difference 0.12 m/s, 95 % CI: 0.05 – 0.19). Rural participants demonstrated better improvements in grip strength at the 12 month (rural-urban difference -2.59 kg, 95 % CI: -3.91 - -1.27) and language function (rural-urban difference -0.38, 95 % CI: -0.68 - -0.09). Frailty reduction was more pronounced in urban areas at the 12 month (−0.21, 95 % CI: -0.38 - -0.03, p = 0.025), but showed minimal change in the rural participants.
CONCLUSION: Rural-urban disparities influence the effectiveness of multidomain interventions. Tailored strategies are needed to optimize health outcomes across diverse settings.
CITATION:
Min-Yin Ho ; Wei-Ju Lee ; Ko-Han Yen ; Chih-Kuang Liang ; Li-Ning Peng ; Ming-Hsien Lin ; Ching-Hui Loh ; Fei-Yuan Hsiao ; Liang-Kung Chen (2025): Tailoring multidomain intervention programs to reduce cognitive and physical decline in older adults: Examining rural-urban differences in a nationwide cluster-randomized controlled trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100231
TARGETING COGNITIVE AGING WITH CURCUMIN SUPPLEMENTATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Lirong Yu, Na Li, Bin Li, Kaisy Xinhong Ye, Jiuyu Guo, Jiatong Shan, Luwen Cao, Mei Song, Yanyu Wang, Tih-Shih Lee, Andrea B Maier, Lei Feng
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Cognitive aging is a growing public health concern, and curcumin, a bioactive compound derived from turmeric, has been proposed as a potential intervention to support cognitive function due to its anti-inflammatory and antioxidant properties.
OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effects of curcumin on cognitive outcomes related to aging.
METHODS: A comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus was conducted to identify studies published up to June 18, 2024, including both in vivo preclinical animal studies and randomized controlled trials (RCTs) assessing curcumin's effects on cognitive function. In vivo animal studies using Alzheimer’s disease (AD) models and RCTs in human participants were included. Data were extracted and analyzed using meta-analytic techniques.
RESULTS: In preclinical in vivo murine studies (n = 25; total animals = 572), curcumin consistently improved both acquisition memory (SMD = -1.78, 95 % CI: -2.12 to -1.43) and retention memory (SMD = 2.36, 95 % CI: 1.72 to 3.00) in rodent models of AD. Ten human studies include 531 participants. Overall, curcumin showed no significant effect on global cognitive outcomes compared to placebo (SMD = 0.14, 95 % CI: -0.78 to 1.07). Subgroup analyses revealed significant improvements in working memory (SMD = 1.01, 95 % CI: 0.15 to 1.87) and processing speed (SMD = 0.37, 95 % CI: 0.07 to 0.67). The incidence of adverse events was higher in the curcumin group than in the control group.
CONCLUSIONS: Preclinical in vivo evidence suggests curcumin enhances cognitive function in AD models. However, human studies show inconsistent findings with benefits limited to specific cognitive domains. Larger, well-designed randomized controlled trials are needed to establish curcumin's efficacy and safety in cognitive aging.
CITATION:
Lirong Yu ; Na Li ; Bin Li ; Kaisy Xinhong Ye ; Jiuyu Guo ; Jiatong Shan ; Luwen Cao ; Mei Song ; Yanyu Wang ; Tih-Shih Lee ; Andrea B Maier ; Lei Feng (2025): Targeting cognitive aging with curcumin supplementation: A systematic review and meta-analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100248
ASSOCIATION OF VITAMIN B12 DEFICIENCY IN A DEMENTIA COHORT WITH HIPPOCAMPAL ATROPHY ON MRI
Asako Ueno, Tadanori Hamano, Miwako Nagata, Tomohisa Yamaguchi, Yoshinori Endo, Soichi Enomoto, Hirohiko Kimura, Masamichi Ikawa, Osamu Yamamura, Daiki Yamanaka, Yohei Kimura, Yasunari Nakamoto, Yasuhiro Nishiyama
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Vitamin deficiencies have been reported to cause brain atrophy. Hippocampal atrophy has been well reported in patients with dementia including Alzheimer’s disease.
OBJECTIVES: To investigate the association between hippocampal atrophy and vitamin deficiency
DESIGN: Cross sectional study.
SETTING: Three sites in one country.
PARTICIPANTS: Overall, 567 patients who visited an outpatient dementia clinic and underwent MRI-VSRAD (Voxel-Based Specific RegionalAnalysis System for Alzheimer's Disease) were included in this study.
INTERVENTION: Patients with a hippocampal atrophy Z-score of < 2 were classified as normal (n = 323), and those with a Z-score of ≥ 2 were diagnosed with hippocampal atrophy (n = 244).
MEASUREMENTS: Vitamin B12, folic acid, vitamin B1, homocysteine, HbA1c, and creatinine levels were measured and their association with hippocampal atrophy was assessed. Age, MMSE (Mini Mental State Examination), and hippocampal atrophy were also evaluated.
RESULTS: In the hippocampal atrophy group, the frequency of vitamin B12 deficiency was higher (p < 0.022), MMSE score was lower (p < 0.0001), and age was higher (p < 0.0001) than that in the normal group (Mann-Whitney U test). Patients with vitamin B12 deficiency (odds ratio, 3.46) and low MMSE score (odds ratio, 2.24) had an increased risk of hippocampal atrophy.
CONCLUSION: Vitamin B12 deficiency was associated with hippocampal atrophy detected by VSRAD analysis. Therefore, early vitamin B12 supplementation should be considered in patients with deficiencies to reduce dementia risk.
CITATION:
Asako Ueno ; Tadanori Hamano ; Miwako Nagata ; Tomohisa Yamaguchi ; Yoshinori Endo ; Soichi Enomoto ; Hirohiko Kimura ; Masamichi Ikawa ; Osamu Yamamura ; Daiki Yamanaka ; Yohei Kimura ; Yasunari Nakamoto ; Yasuhiro Nishiyama (2025): Association of vitamin B12 deficiency in a dementia cohort with hippocampal atrophy on MRI. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100265
A MULTIMODAL LIFESTYLE INTERVENTION COMPLEMENTED WITH EPIGALLOCATECHIN GALLATE TO PREVENT COGNITIVE DECLINE IN APOE- Ɛ4 CARRIERS WITH SUBJECTIVE COGNITIVE DECLINE: A RANDOMIZED, DOUBLE-BLINDED CLINICAL TRIAL (PENSA STUDY)
Laura Forcano, Natalia Soldevila-Domenech, Anna Boronat, Gonzalo Sánchez-Benavides, Albert Puig-Pijoan, Thais Lorenzo, Ana Aldea-Perona, Marc Suárez-Calvet, Aida Cuenca-Royo, Juan Domingo Gispert, Maria Gomis-Gonzalez, Carolina Minguillón, Patrícia Diaz-Pellicer, Karine Fauria, Iris Piera, Klaus Langohr, Mara Dierssen, Nieves Pizarro, Esther Mur-Gimeno, Oriol Grau-Rivera, José Luis Molinuevo, Rafael de la Torre, the PENSA working group
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: The potential of dietary compounds to enhance the effects of multimodal lifestyle interventions (MLIs) on cognition in individuals at high risk of cognitive impairment remains unclear.
OBJECTIVES: To assess whether the addition of a green tea extract enriched with epigallocatechin-3-gallate (EGCG) enhances the effects of an MLI.
DESIGN: Double-blind, randomized, two-arm, and placebo-controlled trial. Exploratory comparisons were made with a non-randomized group (NRG) receiving healthy lifestyle recommendations. Setting: Population-based study conducted in Barcelona, Spain
PARTICIPANTS: APOE-ɛ4 carriers aged 60-80 with subjective cognitive decline.
INTERVENTION: A 12-month intensive MLI including dietary counseling, guided physical activity, and cognitive stimulation, combined with EGCG (5-6 mg/kg) or placebo, followed by a 3-month washout.
MEASUREMENTS: Primary endpoint was change in the modified Preclinical Alzheimer Cognitive Composite (PACC-exe) score.
RESULTS: 129 participants (65.1% 84 women, aged 66.7±5.5 years) were enrolled (52 MLI+EGCG, 52 MLI+placebo and 25 NRG), with126 (97.7%) included in the modified intention-to-treat analysis. After 12 months, no statistically significant difference was observed between MLI+EGCG and MLI+placebo in the PACC-exe (adjusted mean difference [AMD]: 0.12; 95%CI: -0.01, 0.24; p=0.061). However, participants in the MLI+EGCG group were 2.6 times more likely to show a reliable cognitive improvement. In exploratory analyses following a 3-month washout, the MLI+EGCG group showed significant cognitive benefits compared to the MLI+placebo (AMD: 0.19; 95%CI: 0.06, 0.32; p=0.005). Exploratory comparisons with the NRG also suggested greater gains in cognition and dementia risk reduction in both MLI groups, particularly with EGCG.
CONCLUSIONS: While the primary outcome was not met, this proof-of-concept trial suggests that combining MLIs with EGCG warrants further investigation in larger, confirmatory studies.
CITATION:
Laura Forcano ; Natalia Soldevila-Domenech ; Anna Boronat ; Gonzalo Sánchez-Benavides ; Albert Puig-Pijoan ; Thais Lorenzo ; Ana Aldea-Perona ; Marc Suárez-Calvet ; Aida Cuenca-Royo ; Juan Domingo Gispert ; Maria Gomis-Gonzalez ; Carolina Minguillón ; Patrícia Diaz-Pellicer ; Karine Fauria ; Iris Piera ; Klaus Langohr ; Mara Dierssen ; Nieves Pizarro ; Esther Mur-Gimeno ; Oriol Grau-Rivera ; José Luis Molinuevo ; Rafael de la Torre ; the PENSA working group (2025): A multimodal lifestyle intervention complemented with epigallocatechin gallate to prevent cognitive decline in APOE- ɛ4 carriers with Subjective Cognitive Decline: a randomized, double-blinded clinical trial (PENSA study). The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100271
POLYUNSATURATED FATTY ACIDS, APOE GENOTYPES, AND DEMENTIA INCIDENCE AND MORTALITY AMONG HYPERTENSIVE ADULTS
Yubo Zhang, Jindi Li, Shaohui Liu, Quanhong Chen, Xuexiu Wang, Sisi He, Yadong Wei, Yunfeng Zou, Yunan Xu, Lijun Wang, Hao Chen
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Individuals with hypertension have an elevated risk of dementia. The potential protective effects of dietary polyunsaturated fatty acids (PUFAs) against dementia remain unclear. In this study, we investigate associations between blood PUFA levels and dementia outcomes, while considering the genetic predisposition among hypertensive adults.
METHODS: We employed data from UK Biobank and a prospective cohort of 123,235 hypertensive participants aged 40–69 years were included for the analysis (2006–2022). Cox proportional hazards models adjusting for covariates were applied to assess the associations of blood levels of docosahexaenoic acid (DHA), N3FA, N6FA, linoleic acid (LA), total PUFA, and the N6FA/N3FA ratio with incident dementia, dementia mortality, and all-cause mortality. The analyses were also stratified by polygenic risk scores (PRS) or APOE genotypes.
RESULTS: Higher levels of DHA (HR 0.41, 95 % CI 0.27–0.62), N3FA, LA, N6FA, and total PUFA were associated with significantly reduced dementia incidence (P < 0.001). In contrast, a higher N6FA/N3FA ratio was linked to increased dementia risk. Similar trends were observed for mortality. APOE genotypes, rather than PRS, modified PUFA–dementia associations: individuals with low-to-moderate APOE risk showed greater protective effects of high PUFA levels compared to those with high-risk genotypes.
CONCLUSIONS: Among hypertensive adults, higher PUFA levels are associated with reduced risks of dementia and mortality. An imbalanced N6FA/N3FA ratio increases risk, while APOE genotypes significantly modify PUFA-related dementia outcomes.
CITATION:
Yubo Zhang ; Jindi Li ; Shaohui Liu ; Quanhong Chen ; Xuexiu Wang ; Sisi He ; Yadong Wei ; Yunfeng Zou ; Yunan Xu ; Lijun Wang ; Hao Chen (2025): Polyunsaturated fatty acids, APOE genotypes, and dementia incidence and mortality among hypertensive adults. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100297
CAUSAL RELATIONSHIP AND MEDIATING ROLE BETWEEN DEPRESSION AND COGNITIVE PERFORMANCE
Xinyu Hao, Fuyang Cao, Ziyao Xu, Shaohua You, Tianyue Mi, Lei Wang, Yongxin Guo, Zhuoning Zhang, Jiangbei Cao, Jingsheng Lou, Yanhong Liu, Xianyang Chen, Zhikang Zhou, Weidong Mi, Li Tong
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Recent studies have increasingly emphasized the robust correlation between depression and cognitive function. However, it remains unclear whether this relationship is causal or merely coincidental. To address this uncertainty, we conducted two-sample bidirectional Mendelian randomization (MR) analyses to investigate the connection between depression and cognitive performance.
METHODS: We sourced genome-wide association study (GWAS) data for depression (NSNPs=21,306,230) from the FinnGen (R10) and for cognitive performance (NSNPs=10,049,954) from the IEU GWAS database. Causal effects employed methodologies such as Inverse variance weighted (IVW), weighted median, MR Egger, simple mode and weighted mode. Two-step analysis determined the contribution of the mediator variable to the outcomes. To determine stability and reliability, sensitivity analyses were performed that included an assessment of heterogeneity, horizontal pleiotropy, and the leave-one-out techniques.
RESULTS: This MR analysis identified 8 independent significant SNPs associated with depression and 81 SNPs linked to cognitive performance. Our findings revealed that depression increases the risk of developing deteriorating cognitive performance (IVW β, -0.11; 95 % confidence interval (CI), -0.18 – -0.05; PIVW value= 5.97E-04). Conversely, cognitive performance decline could also predispose individuals to depression [odds ratio (OR)IVW, 0.85; 95 % CI, 0.76 – 0.95; PIVW value=0.004]. Multivariate MR analysis confirmed the robustness of this bidirectional association. A two-step MR mediation analysis indicated that the pathway from depression to cognitive performance is mediated by pain, with a mediation effect size of -0.022 and a mediation ratio of 28.95 %. The pathway from cognitive performance to depression is mediated by frailty, with a mediation effect value of -0.028, representing 22.40 % of the mediation proportion.
CONCLUSION: A two-way causal relationship between depression and cognitive performance, with pain and frailty being mediating factors, respectively. Future research should prioritize mechanistic studies, targeted interventions, and personalized approaches to disentangle and mitigate the bidirectional effects of depression and cognitive performance.
CITATION:
Xinyu Hao ; Fuyang Cao ; Ziyao Xu ; Shaohua You ; Tianyue Mi ; Lei Wang ; Yongxin Guo ; Zhuoning Zhang ; Jiangbei Cao ; Jingsheng Lou ; Yanhong Liu ; Xianyang Chen ; Zhikang Zhou ; Weidong Mi ; Li Tong (2025): Causal relationship and mediating role between depression and cognitive performance. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100196
TRAJECTORIES OF CARDIORESPIRATORY FITNESS MEASURED BY METABOLIC EQUIVALENTS AND THE RISK OF ALZHEIMER\'S AND RELATED DEMENTIAS
Edward Zamrini, Yan Cheng, Peter Kokkinos, Charity J Morgan, Charles Faselis, Helen M Sheriff, Yijun Shao, Xuemei Sui, Ali Ahmed, Qing Zeng
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Higher fitness levels have been reported to protect against Alzheimer's Disease and Related Dementias (ADRD). However, the association between changes in fitness over time and ADRD risk remains unknown. This study aims to identify clusters of metabolic equivalents (METs) trajectories and examine their correlation with incident ADRD.
METHODS: A retrospective cohort study was conducted among Veterans with ≥3 standardized exercise treadmill tests (ETT) between 2000 and 2017. The exposure was change in fitness expressed in metabolic equivalents (METs). METs are based on treadmill speed, grade, and time. One MET is equivalent to 3.5 ml per kg of body weight per minute. The outcome was incident ADRD after the final ETT test, identified by diagnosis codes. Standardized METs scores were generated using mean and standard deviation for each age and sex stratum. Latent class growth analysis (LCGA) identified trajectory clusters. We assessed the association between clusters and ADRD using unadjusted Kaplan-Meier curves (overall and by age groups) and a multivariate Cox regression model adjusted for baseline characteristics at the first ETT.
RESULTS: A total of 75,851 veterans were included. The average number of ETTs was 4.0 ± 1.8, with the average time gap of 6.5 ± 3.8 years between first and last test. We identified five trajectory clusters: Group 1 (n = 22,485), Group 2 (n = 22,694), Group 3 (n = 6691), Group 4 (n = 19,386), and Group 5 (n = 4595). All groups, except for Group 3, showed a stable and slight improvement or decline over time, differing only in their initial standardized METs scores: Group 5 had the highest initial score, Group 1 had the lowest initial score, while Group 3 started out with a score almost as high as Group 4 and dropped to as low as Group 1. Compared to Group 1, Group 3 had a 12 % reduced risk of developing ADRD (HR = 0.88; 95 % CI: 0.77 – 1.01; p = 0.0660), with a greater reduction than Group 2 (10 %) but less than Group 4 (17 %) or Group 5 (24 %).
DISCUSSION: Our findings underscore the potential benefits of maintaining fitness to reduce the risk of ADRD with age. Although declining fitness levels are associated with an increased risk, the initial higher baseline fitness provides a degree of ongoing protection against ADRD.
CITATION:
Edward Zamrini ; Yan Cheng ; Peter Kokkinos ; Charity J Morgan ; Charles Faselis ; Helen M Sheriff ; Yijun Shao ; Xuemei Sui ; Ali Ahmed ; Qing Zeng (2025): Trajectories of Cardiorespiratory Fitness Measured by Metabolic Equivalents and the Risk of Alzheimer's and Related Dementias. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100222
HOUSEHOLD FUEL USE AND MOTORIC COGNITIVE RISK SYNDROME AMONG OLDER ADULTS: EVIDENCE FROM COHORT STUDY AND LIFE COURSE ANALYSIS
Guanghui Cui, Shaojie Li, Weiwei Li, Xuezhi Zhang
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Motoric cognitive risk syndrome (MCRS) is a predementia syndrome, and its prevention is valuable for reducing the incidence of dementia. However, few studies have focused on the association between indoor air pollution caused by household cooking fuel use and MCRS. This study aimed to investigate whether clean cooking fuel use is associated with reduced MCRS risk and whether the timing of clean fuel adoption across the life span is associated with MCRS prevalence.
METHODS: We used data from the China Health and Retirement Longitudinal Study. A prospective cohort analysis (n = 4251) examined baseline fuel use (2011) and incident MCRS over four years. A cross-sectional life course analysis (n = 6964) linked retrospective fuel use histories (2014 life history survey) to MCRS status in 2015. Modified Poisson regression was used to estimate relative risks (RRs) and 95 % confidence intervals (CIs), adjusting for covariates.
RESULTS: In the cohort study, clean fuel use at baseline was associated with a reduced risk of MCRS (RR = 0.76; 95 % CI: 0.61–0.96). Lower risks were also observed among participants who transitioned from solid to clean fuels and those who consistently used clean fuels. In the life course analysis, clean fuel adoption in early or middle adulthood was linked to lower MCRS prevalence.
CONCLUSION: Clean fuel use for cooking and transitioning from solid to clean fuels decreases MCRS risk among older adults. Moreover, earlier adoption of clean cooking fuels is associated with a lower prevalence of MCRS in later life.
CITATION:
Guanghui Cui ; Shaojie Li ; Weiwei Li ; Xuezhi Zhang (2025): Household fuel use and motoric cognitive risk syndrome among older adults: Evidence from cohort study and life course analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100227
THE COUPLING OF GLOBAL BRAIN ACTIVITY AND CEREBROSPINAL FLUID FLOW AS A POTENTIAL PREDICTIVE MARKER OF BRAIN AMYLOID-Β ACCUMULATION
Yuya Tanaka, Koji Kamagata, Yuya Saito, Kaito Takabayashi, Rinako Iseki, Wataru Uchida, Christina Andica, Akifumi Hagiwara, Akihiko Wada, Toshiaki Akashi, Osamu Abe, Shigeki Aoki, Alzheimer’s Disease Neuroimaging Initiative
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Impaired cerebrospinal fluid (CSF) clearance is thought to contribute to amyloid-β (Aβ) accumulation in Alzheimer’s disease (AD). Global brain activity–CSF flow coupling (gBOLD–CSF coupling), measured through resting-state functional MRI, reflects CSF clearance capacity. A higher coupling value indicates weaker coupling. Its potential as a predictive marker for Aβ accumulation remains unclear.
OBJECTIVES: This study aims to determine whether weaker gBOLD–CSF coupling precedes Aβ accumulation in cognitively normal, Aβ-negative individuals and to explore its predictive potential for amyloid conversion.
DESIGN: A longitudinal observational study using Alzheimer’s Disease Neuroimaging Initiative (ADNI) data.
SETTING: Data from ADNI-participating sites.
PARTICIPANTS: 16 cognitively normal participants, initially Aβ-negative: seven fast-converters (transitioned to Aβ-positive within two years) and nine slow-converters (remained Aβ-negative for at least two years).
MEASUREMENTS: gBOLD–CSF coupling was calculated as the Pearson correlation coefficient between global Blood-Oxygen-Level-Dependent (BOLD) and CSF inflow signals. Group differences in gBOLD–CSF coupling were analyzed, along with partial correlation analyses between gBOLD–CSF coupling and annual changes in Aβ biomarkers and cognitive scores.
RESULTS: Fast-converters showed significantly higher gBOLD–CSF coupling values, indicating weaker coupling (Cohen’s d = 1.76, p = 0.012). Coupling values positively correlated with annual changes in Aβ-PET SUVR (r = 0.594, p = 0.054) and negatively with MoCA scores (r = −0.654, p = 0.021).
CONCLUSION: Weaker gBOLD–CSF coupling precedes brain Aβ accumulation, indicating its potential as a predictive marker for amyloid conversion. Future studies should refine clinical thresholds for early intervention strategies in AD prevention.
CITATION:
Yuya Tanaka ; Koji Kamagata ; Yuya Saito ; Kaito Takabayashi ; Rinako Iseki ; Wataru Uchida ; Christina Andica ; Akifumi Hagiwara ; Akihiko Wada ; Toshiaki Akashi ; Osamu Abe ; Shigeki Aoki ; Alzheimer’s Disease Neuroimaging Initiative (2025): The coupling of global brain activity and cerebrospinal fluid flow as a potential predictive marker of brain amyloid-β accumulation. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100228
PSYCHOSOCIAL STRESSORS AND COGNITIVE FUNCTION: AN ANALYSIS USING DATA FROM THE ENGLISH LONGITUDINAL STUDY OF AGEING
Jiahao Li, Natalia Ortí-Casañ, Irem Bayraktaroglu, Giulia Mozzanica, Feng Zhang, Jocelien D.A. Olivier, Ulrich L.M. Eisel
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Growing evidence suggests that psychosocial stressors—such as financial strain, caregiving responsibilities, disability, and limiting long-term illnesses—may contribute to accelerated cognitive decline in older adults. However, the heterogeneity of stressor profiles and their distinct impact on specific cognitive domains remain poorly understood.
OBJECTIVE: To examine the associations between varying burdens of psychosocial stressors and cognitive function over a 10-year period using data from the English Longitudinal Study of Ageing (ELSA).
METHODS: We used longitudinal data from wave 4 (2008–2009) to wave 9 (2018–2019) of ELSA, comprising 10,893 participants aged ≥50 years at baseline who had valid measurements of psychosocial stressors and cognitive outcomes. Psychosocial stressors—financial strain, caregiving, disability, and limiting long-term illness—were assessed as binary indicators and summed into three categories (No Stressors, One Stressor, Multiple Stressors). Cognitive function was assessed using an overall global cognition score and scores of three specific domains: memory, executive function, and orientation. Baseline associations were examined via multiple linear regression, while linear mixed-effects models evaluated longitudinal trajectories of cognitive change. All models were progressively adjusted for demographic, lifestyle, and clinical covariates.
RESULTS: At baseline, participants reporting multiple stressors (18.2 % of the sample) had significantly lower global cognitive and executive function scores compared to those with no stressors (43.3 %). Over the 10-year follow-up, a higher stress burden predicted faster declines in global cognition, memory, and executive function. These associations remained robust after adjusting for sociodemographic characteristics, health behaviors, and chronic conditions. Random intercept and random slope models yielded consistent findings, indicating a dose–response relationship between stress burden and cognitive deterioration.
CONCLUSION: Older adults experiencing multiple psychosocial stressors face an elevated risk of both lower initial cognitive function and accelerated decline over time. These findings underscore the importance of identifying and mitigating modifiable stressors—such as financial strain and caregiving demands—to potentially preserve cognitive health in later life. Interventions tailored to individuals with higher stress burdens may be especially beneficial in slowing cognitive deterioration.
CITATION:
Jiahao Li ; Natalia Ortí-Casañ ; Irem Bayraktaroglu ; Giulia Mozzanica ; Feng Zhang ; Jocelien D.A. Olivier ; Ulrich L.M. Eisel (2025): Psychosocial stressors and cognitive function: An analysis using data from the English longitudinal study of ageing. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100232
SYNERGISTIC EFFECTS OF MULTIPLE PATHOLOGICAL PROCESSES ON ALZHEIMER\'S DISEASE RISK: EVIDENCE FOR AGE-DEPENDENT STROKE INTERACTIONS
Fen Liu, Xuesong Xia, Chengjie Zheng, Feng Liu, Min Jiang
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Alzheimer's disease (AD) pathogenesis involves complex interactions between multiple neuropathological processes, yet traditional approaches focus on individual markers. The cumulative effects of multiple pathologies and their interactions with cerebrovascular compromise and age remain poorly understood. This study aimed to develop a comprehensive Pathological Burden Score (PBS) and examine its relationship with AD risk, including interactions with stroke history and age.
METHODS: We analyzed 11,308 participants from the National Alzheimer's Coordinating Center database. A PBS was constructed integrating six neuropathological domains: Braak neurofibrillary tangle staging, CERAD neuritic plaque density, Thal amyloid-β phasing, stroke history, white matter rarefaction severity, and cerebral atrophy severity (range 0–16 points). PBS was categorized into four burden levels: low (0–4), moderate (5–8), high (9–12), and very high (13–16). Multivariable logistic regression examined associations between PBS categories and AD risk, with formal interaction testing for stroke × PBS effects. Age-stratified analyses were conducted using a 75-year cutpoint.
RESULTS: A clear dose-response relationship was observed between PBS and AD risk, with very high burden conferring over 5-fold increased odds compared to low burden. Significant stroke × PBS interaction was detected (interaction OR 1.23, p < 0.001), with stroke amplifying pathological burden effects. Among participants with very high burden, AD risk was 92.5 % in stroke patients versus 24.1 % in non-stroke patients. Age-dependent effects were profound: younger participants (<75 years) with high burden plus stroke showed 18.67-fold increased odds, while older participants (≥75 years) with equivalent burden showed 7.89-fold increased odds.
CONCLUSIONS: Cumulative pathological burden demonstrates a strong dose-response relationship with AD risk, significantly amplified by stroke history. The pronounced age-dependent effects highlight the need for age-specific prevention strategies, with particular emphasis on aggressive vascular risk management in younger populations. These findings support comprehensive pathological burden assessment for enhanced risk stratification and personalized dementia care approaches.
CITATION:
Fen Liu ; Xuesong Xia ; Chengjie Zheng ; Feng Liu ; Min Jiang (2025): Synergistic effects of multiple pathological processes on Alzheimer's disease risk: Evidence for age-dependent stroke interactions. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100268
STRESS INTERNALIZATION IS A TOP RISK FOR AGE-ASSOCIATED COGNITIVE DECLINE AMONG OLDER CHINESE IN THE U.S
Michelle H Chen, Yiming Ma, Charu Verma, Stephanie Bergren, William T Hu
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Behavioral and sociocultural factors are often examined in population-based studies as independent variables, yet latent factors often influence multiple behaviors all at once. This may be especially true in immigrant populations living in or near ethnic enclaves. Better characterization of internal or external factors underlying multiple behaviors is critical to modify the root causes of health-related behaviors.
OBJECTIVES: To identify inter-relatedness of multiple internal (acculturation, behavior, well-being) and external (neighborhood & community) characteristics, as well as their influence on age-associated cognitive decline in a large group of non-demented older Chinese Americans living in the Chicago metropolitan area.
SETTING: Secondary data analysis of the Population Study of ChINese Elderly (PINE).
PARTICIPANTS: 1528 non-demented older Chinese Americans (aged 60+) who attended three waves of PINE.
DESIGN: Longitudinal cohort study.
INTERVENTION(S): Not applicable.
MEASUREMENTS: Three psychobehavioral and 3 sociocultural factors were included in factor analysis for independent variables; Chinese versions of the Mini-Mental State Examination, East Boston Memory Test, Digit Span Backward, and oral Symbol Digit Modalities Test were included in principal component analysis to derive dependent variables.
RESULTS: Factor analysis identified three main behavioral/sociocultural constructs: stress internalization, neighborhood/community cohesion, and external stress alleviation. Among these, only stress internalization – consisting of greater perceived stress, greater hopelessness, and lower conscientiousness – was associated with longitudinal decline in memory, while none with decline in executive functioning. Neither acculturation nor activity engagement was related to longitudinal decline in memory or executive functioning, even though participants with greater acculturation or activity engagement had better baseline cognitive performance.
CONCLUSIONS: Only the factor underlying stress processing, hopelessness, and conscientiousness was associated with rates of longitudinal memory decline in this older non-demented Chinese American cohort. These maladaptive traits have been linked to the Asian model minority stereotype but all the same potentially modifiable. Limitations include potential selection bias, potential cultural inappropriateness of the measures, and limited cognitive test battery and clinical information.
CITATION:
Michelle H Chen ; Yiming Ma ; Charu Verma ; Stephanie Bergren ; William T Hu (2025): Stress internalization is a top risk for age-associated cognitive decline among older Chinese in the U.S. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100270
ASSOCIATIONS OF CARDIOVASCULAR HEALTH ASSESSED BY LIFE’S CRUCIAL 9 WITH INCIDENT CARDIOVASCULAR DISEASE AND DEMENTIA: A PROSPECTIVE COHORT STUDY
Yiwen Dai, Yuling Liu, Yang Pan, Jingya Ma, Jie Liang, Wenya Zhang, Xuyang Diao, Menghan Zhu, Xinqing Yang, Darui Gao, Yanyu Zhang, Mengmeng Ji, Yichi Zhang, Wuxiang Xie, Fanfan Zheng
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: The associations of the renewed cardiovascular health (CVH) assessed by Life’s Crucial 9 (LC9), which consisted of Life’s Essential 8 (LE8) and psychological health, with incident cardiovascular disease (CVD) and dementia remained unexplored.
OBJECTIVES: This study aims to investigate the associations and determine whether LC9 has a higher discrimination ability than LE8 in predicting incident CVD and dementia.
DESIGN, SETTING, AND PARTICIPANTS: This study was a prospective population-based cohort study using data from the UK Biobank.
MEASUREMENTS: LC9 was assessed as American Heart Association recommended. Incident CVD and dementia were based on self-reported data, hospital inpatient records, and death register records.
RESULTS: Of 289,649 included participants, 137,480 (47.5 %) were male, and the mean age was 56.6 ± 8.1 years. Compared with participants having low LC9, those having moderate or high LC9 had lower risks of incident CVD (moderate: 0.46 [0.43–0.48]; high: 0.25 [0.23–0.27]; p for trend <0.001) and dementia (moderate: 0.57 [0.50–0.64]; high: 0.45 [0.39–0.52]; p for trend <0.001) after multivariate adjustment. Both the LE8 and LC9 achieved good discriminative performance for incident CVD (LE8 Harrell C-statistic= 0.7138 vs. LC9 Harrell C-statistic=0.7144, p = 0.136); the net reclassification improvement was estimated at 0.07 % (p = 0.749), and integrated discrimination improvement was estimated at 0.009 (p < 0.001). The results for dementia showed similar patterns.
CONCLUSIONS AND RELEVANCE: Optimal LC9 was associated with lower risks of incident CVD and dementia. Although psychological health is essential for preventing CVD and dementia, including it into CVH's evaluation criteria did not significantly improve CVH's predictive performance.
CITATION:
Yiwen Dai ; Yuling Liu ; Yang Pan ; Jingya Ma ; Jie Liang ; Wenya Zhang ; Xuyang Diao ; Menghan Zhu ; Xinqing Yang ; Darui Gao ; Yanyu Zhang ; Mengmeng Ji ; Yichi Zhang ; Wuxiang Xie ; Fanfan Zheng (2025): Associations of cardiovascular health assessed by life’s crucial 9 with incident cardiovascular disease and dementia: A prospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100273
UNDERDETECTION OF NEUROCOGNITIVE DISORDERS IN SOUTHERN ITALY: EVIDENCE FROM THE SALENTO REGION
Davide Vilella, Daniele Urso, Agnese Valguarnera, Giuseppe Volpe, Valentina Gnoni, Eleonora Rollo, Alessia Giugno, Marcella Caggiula, Brigida Coluccia, Annamaria Mauro, Roberta Barone, Miriam Accogli, Marzia Leopizzi, Alessandro Introna, Marco Musio, Stefano Giannoni-Luza, Giancarlo Logroscino
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Neurocognitive disorders, including dementia and mild cognitive impairment, are increasingly prevalent, demanding efficient detection and management strategies.
OBJECTIVES: This study is part of the Puglia Region’s initiative under the Italian Dementia National Plan (DNP) and aimed to assess the capacity of the Lecce province healthcare system to identify new neurocognitive disorders cases by comparing observed cases with expected rates derived from meta-analyses and Global Burden of Disease estimates.
DESIGN: Using complete case ascertainment across 10 hospital-based and community centers, a total of 857 incident cases were identified in one year, including 441 Minor neurocognitive disorders (51.46 %) and 416 major neurocognitive disorders cases (48.54 %).
SETTING: Public Centers for Cognitive Disorders and Dementia (CCDDs) across hospital and community services in the Lecce province, Southern Italy.
PARTICIPANTS: Eligible participants included all individuals aged between 65 and 89 residing in the Lecce province who received a diagnosis of neurocognitive disorder. 857 participants were enrolled (519 females – 338 males).
MEASUREMENTS: Incident cases of neurocognitive disorder, both minor and major, accordingly to DSM-5 criteria.
RESULTS: Only 10.65 % of expected major neurocognitive disorders and 7.24 % of expected minor neurocognitive disorders cases were detected, with significant age and sex disparities, with higher underdetection rates in females. Detection rates declined with advancing age, with the observed-to-expected ratio for major neurocognitive disorders falling from 18.23 % in individuals aged 65–69 years to just 5.24 % in those aged 85–89 years. These findings were validated against Global Burden of Disease estimates.
CONCLUSIONS: This study highlights the critical gaps in detecting neurocognitive disorders, particularly in older adults and prodromal stages such as minor neurocognitive disorders, where early intervention could yield the greatest benefits. The findings underscore the urgent need for targeted reforms to improve e diagnostic pathways and better align healthcare systems with emerging disease-modifying therapies and preventive strategies.
CITATION:
Davide Vilella ; Daniele Urso ; Agnese Valguarnera ; Giuseppe Volpe ; Valentina Gnoni ; Eleonora Rollo ; Alessia Giugno ; Marcella Caggiula ; Brigida Coluccia ; Annamaria Mauro ; Roberta Barone ; Miriam Accogli ; Marzia Leopizzi ; Alessandro Introna ; Marco Musio ; Stefano Giannoni-Luza ; Giancarlo Logroscino (2025): Underdetection of neurocognitive disorders in Southern Italy: Evidence from the Salento region. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100295
TRAJECTORIES OF MUSCLE STRENGTH AND PHYSICAL PERFORMANCE PRECEDING DEMENTIA IN OLDER US AND EUROPEAN POPULATIONS
Youjin Jiang, Yi Ding, Qiuyu Cao, Xianglin Wu, Xiaoran Li, Yu Xu, Zhiyun Zhao, Min Xu, Jieli Lu, Tiange Wang, Guang Ning, Weiqing Wang, Yufang Bi, Yuchen Xu, Mian Li
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: The association between muscle function and dementia risk remains elusive, as studies suggest that impaired muscle function may act as both a risk factor for and a consequence of dementia, hindering causal inference.
OBJECTIVES: We aimed to clarify the temporal relationship between muscle function and incident dementia by investigating non-linear trajectories of muscle function in the years preceding dementia onset in older US and European populations.
DESIGN: Case-control study.
SETTING: Data were combined from the English Longitudinal Study of Ageing (ELSA, 2004–2018, waves 2–9), Health and Retirement Study (HRS, 2004–2018, waves 7–14), and Survey of Health, Ageing and Retirement in Europe (SHARE, 2004–2017, waves 1–7).
PARTICIPANTS: For handgrip strength analysis, 18,335 participants aged 60 and older were included from the ELSA, HRS, and SHARE cohorts. For gait speed analysis, 11,690 participants aged 60 and older were included from the ELSA and HRS cohorts.
MEASUREMENTS: Muscle strength was assessed by handgrip strength using a Smedley dynamometer, and physical performance was evaluated by gait speed using the Timed 8-Foot Walk test, with assessments conducted biennially or quadrennially. Dementia was diagnosed using self-reported physician diagnosis and cognitive-functional assessments. Trajectories of muscle strength and physical performance were analyzed on a backward timescale using latent-process mixed models within a nested case-control design.
RESULTS: Significant differences in muscle function trajectories were observed between cases and controls 12 and 13 years prior to dementia onset (handgrip strength: coefficient [SE], -0.23 [0.05], P < 0.001; gait speed: coefficient [SE], -0.24 [0.08], P = 0.003). The pathological trajectories of handgrip strength and gait speed revealed periods of acceleration beginning 6 and 8 years prior to diagnosis, respectively. After adjusting for pre-dementia acceleration, greater handgrip (per 1-kg increment) was associated with a modest reduction in dementia risk (hazard ratio, 0.98; 95 % CI, 0.97–0.99), while faster gait speed (per 1-m/s increment) markedly lowered risk (hazard ratio, 0.35; 95 % CI, 0.23–0.53).
CONCLUSIONS: These findings highlight muscle function as a cost-effective tool for early detection and dynamic monitoring of dementia risk and identify it as a modifiable target for prevention. Muscle function may also assist in identifying high-risk groups for preferential enrollment into clinical trials for dementia prevention and treatment.
CITATION:
Youjin Jiang ; Yi Ding ; Qiuyu Cao ; Xianglin Wu ; Xiaoran Li ; Yu Xu ; Zhiyun Zhao ; Min Xu ; Jieli Lu ; Tiange Wang ; Guang Ning ; Weiqing Wang ; Yufang Bi ; Yuchen Xu ; Mian Li (2025): Trajectories of muscle strength and physical performance preceding dementia in older US and European populations. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100296
MULTIMODAL NEUROIMAGING UNVEILS BASAL FOREBRAIN-LIMBIC SYSTEM CIRCUIT DYSREGULATION IN COGNITIVE IMPAIRMENT WITH DEPRESSION: A PATHWAY TO EARLY DIAGNOSIS AND INTERVENTION
Xiaowen Xu, Xiereniguli Anayiti, Peiying Chen, Zhongfeng Xie, Mengling Tao, Yongsheng Xiang, Mingyu Tan, Yingying Liu, Ling Yue, Shifu Xiao, Peijun Wang
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: Alzheimer’s disease (AD) frequently co-occurs with depressive symptoms, exacerbating both cognitive decline and clinical complexity, yet the neural substrates linking this co-occurrence remain poorly understood. We aimed to investigate the role of basal forebrain-limbic system circuit dysregulation in the interaction between cognitive impairment and depressive symptoms, identifying potential biomarkers for early diagnosis and intervention.
METHODS: This cross-sectional study included participants stratified into normal controls (NC), cognitive impairment without depression (CI-nD), and cognitive impairment with depression (CI-D). Multimodal MRI (structural, diffusion, functional, perfusion, iron-sensitive imaging) and plasma biomarkers were analyzed. Machine learning models classified subgroups using neuroimaging features.
RESULTS: CI-D exhibited distinct basal forebrain-limbic circuit alterations versus CI-nD and NC: (1) Elevated free-water fraction (FW) in basal forebrain subregions (Ch123/Ch4, p < 0.04), indicating early neuroinflammation; (2) Increased iron deposition in the anterior cingulate cortex and entorhinal cortex (p < 0.05); (3) Hyperperfusion and functional hyperactivity in Ch123 and amygdala; (4) Plasma neurofilamentlightchain exhibited correlated with hippocampal inflammation in CI-nD (p = 0.03) but linked to basal forebrain dysfunction in CI-D (p < 0.05). Multimodal support vector machine achieved 85 % accuracy (AUC=0.96) in distinguishing CI-D from CI-nD, with Ch123 and Ch4 as key discriminators. Pathway analysis in the CI-D group further revealed that FW-related neuroinflammation in the basal forebrain (Ch123/Ch4) indirectly contributed to cognitive impairment via structural atrophy.
CONCLUSION: We identified a neuroinflammatory-cholinergic pathway in the basal forebrain as an early mechanism driving depression-associated cognitive decline. Multimodal imaging revealed distinct spatiotemporal patterns of circuit dysregulation, suggesting neuroinflammation and iron deposition precede structural degeneration. These findings position the basal forebrain-limbic system circuit as a therapeutic target and provide actionable biomarkers for early intervention in AD with depressive symptoms.
CITATION:
Xiaowen Xu ; Xiereniguli Anayiti ; Peiying Chen ; Zhongfeng Xie ; Mengling Tao ; Yongsheng Xiang ; Mingyu Tan ; Yingying Liu ; Ling Yue ; Shifu Xiao ; Peijun Wang (2025): Multimodal neuroimaging unveils basal forebrain-limbic system circuit dysregulation in cognitive impairment with depression: a pathway to early diagnosis and intervention. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100298
THE EFFICACY AND SAFETY OF ANTI-AMYLOID MONOCLONAL ANTIBODY VERSUS ACETYLCHOLINESTERASE INHIBITOR WITH AN IN-DEPTH ANALYSIS ACROSS GENOTYPES AND DISEASE STAGES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Chih-Wei Hsu, Tien-Wei Hsu, Yu-Chen Kao, Yu-Hsuan Lin, Trevor Thompson, Andre F. Carvalho, Brendon Stubbs, Ping-Tao Tseng, Fu-Chi Yang, Chia-Kuang Tsai, Chia-Ling Yu, Yu-Kang Tu, Chih-Sung Liang
J Prev Alz Dis 2025;8(12)
Show summaryHide summaryBACKGROUND: To date, studies have not compared the efficacy and safety of monoclonal antibodies (mABs) with acetylcholinesterase inhibitors (AChEIs).
METHODS: Five electronic databases were systemic searched from inception to 10 November 2024 for double-blinded randomized controlled trial (RCT) of patients diagnosed with MCI or mild AD treated with mABs or AChEIs for at least 6 months. The primary outcome was change in cognitive function, measured by the Alzheimer's Disease Assessment Scale–cognitive subscale 14-item (ADAS-Cog) and Clinical Dementia Rating Scale–Sum of Boxes (CDR-SOB). The secondary outcomes were acceptability, tolerability, serious adverse events (SAE), and all -cause mortality. For mABs, amyloid-related imaging abnormalities-edema (ARIA-E), and amyloid-related imaging abnormalities-hemorrhage (ARIA-H) were also assessed. Subgroup analyses included (i) MCI versus mild AD; (ii) with versus without concomitant AD medications; and (iii) Apolipoprotein E (ApoE4) carriers versus non-carriers. Data were pooled using a random effects model within a Bayesian framework.
RESULTS: There were 8010 participants (mean age: 71.5 years) across seven mAB trials, and 4993 participants (mean age:70.7 years) in nine AChEI trials. When compared to placebo, only mABs, not AChEIs, were associated with a slower progression of cognitive decline on CDR-SOB (mean difference -0.41 (95 % credible interval -0.61 to -0.22); minimally important difference (MID) -1) and ADAS-Cog (-1.35 (-2.36 to -0.36), MID -2); however, these benefits of mABs did not reach MID across the two cognitive measurements. Besides, mABs were associated with a slower progression of cognitive decline on CDR-SOB (-0.30 (-0.60 to -0.001)) than AChEIs, although mABs and AChEIs did not differ across safety outcomes, including acceptability, tolerability, SAE, and all-cause mortality. Further analysis of mABs indicated that their efficacy did not differ by disease stage, concomitant AD medications, or APOE4 carrier status. However, APOE4 homozygotes carriers were associated with a 5.53-fold (2.48 to 13.07) increased odds of developing ARIA-E compared to non-carriers. Finally, lecanemab demonstrated relatively better efficacy and a more favorable profile on ARIA-E compared to aducanumab and donanemab.
CONCLUSIONS: mABs were associated with a slower progression of cognitive decline than AChEIs; however, this effect did not reach the MID. The incidence of ARIA-E with mABs was associated with APOE4 carrier status and was not indicative of treatment efficacy.
CITATION:
Chih-Wei Hsu ; Tien-Wei Hsu ; Yu-Chen Kao ; Yu-Hsuan Lin ; Trevor Thompson ; Andre F. Carvalho ; Brendon Stubbs ; Ping-Tao Tseng ; Fu-Chi Yang ; Chia-Kuang Tsai ; Chia-Ling Yu ; Yu-Kang Tu ; Chih-Sung Liang (2025): The efficacy and safety of anti-amyloid monoclonal antibody versus acetylcholinesterase inhibitor with an in-depth analysis across genotypes and disease stages: a systematic review and meta-analysis. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100195
COMMENTARY : TREATMENTS FOR ALZHEIMER’S AND THE DECLARATION OF HELSINKI
Timothy Daly, Andi Olluri, Markku Kurkinen
J Prev Alz Dis 2025;8(12)
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CITATION:
Timothy Daly ; Andi Olluri ; Markku Kurkinen (2025): Commentary: Treatments for Alzheimer’s and the declaration of Helsinki. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100260
LETTER TO THE EDITOR: BLOOD-BRAIN BARRIER WATER EXCHANGE AND PARAMAGNETIC SUSCEPTIBILITY ALTERATIONS DURING ANTI-AMYLOID THERAPY: PRELIMINARY MRI FINDINGS
Yuto Uchida, Yuya Kano, Hirohito Kan, Keita Sakurai, Hideyasu Morita, Yoshihiro Akagawa, Noriyuki Matsukawa, Kenichi Oishi
J Prev Alz Dis 2025;8(12)
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CITATION:
Yuto Uchida ; Yuya Kano ; Hirohito Kan ; Keita Sakurai ; Hideyasu Morita ; Yoshihiro Akagawa ; Noriyuki Matsukawa ; Kenichi Oishi (2025): Letter to the Editor: Blood-brain barrier water exchange and paramagnetic susceptibility alterations during anti-amyloid therapy: preliminary MRI findings. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100256
LETTER TO THE EDITOR: COMMENT BY EUROPEAN ALZHEIMER’S DISEASE CONSORTIUM (EADC) INVESTIGATORS ON THE NEGATIVE RECOMMENDATION OF THE CHMP ON THE MARKETING AUTHORIZATION OF DONANEMAB FOR EARLY ALZHEIMER’ S DISEASE
Frank Jessen, Javier Arbizu, Mercé Boada, Karim Bennys, Marina Boban, Katharina Bürger, Andrea Chincarini, Annachiara Cagnin, Peter Paul De Deyn, Emrah Düzel, Sebastiaan Engelborghs, Michael Ewers, Lieza G. Exalto, Wiesje M. van der Flier, Juan Fortea, Kristian Steen Frederiksen, Giovanni B Frisoni, Lutz Frölich, Alejandro J. Garza-Martinez, Timo Grimmer, Bernard Hanseeuw, Jakub Hort, Adrian Ivanoiu, Patrick G Kehoe, Sean P Kennelly, Silke Kern, Stefan Klöppel, Lenka Kraj?ovi?ová, Milica G. Kramberger, Bernadette McGuinness, Patrizia Mecocci, Timo Jan Oberstein, Pierre-Jean Ousset, Claire Paquet, Robert Perneczky, Fabrizio Piazza, Domenico Plantone, Innocenzo Rainero, Guillaume Sacco, Eric Salmon, Isabel Santana, Nikolaos Scarmeas, Anja Schneider, Jonathan M Schott, Eino Solje, Elka Stefanova, Elisabeth Stögmann, Mélanie Strauss, Stanislav Sutovsky, Gunhild Waldemar, Bengt Winblad
J Prev Alz Dis 2025;8(12)
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CITATION:
Frank Jessen ; Javier Arbizu ; Mercé Boada ; Mircea Balasa ; Karim Bennys ; Marina Boban ; Katharina Bürger ; Andrea Chincarini ; Annachiara Cagnin ; Peter Paul De Deyn ; Emrah Düzel ; Sebastiaan Engelborghs ; Michael Ewers ; Lieza G. Exalto ; Wiesje M. van der Flier ; Juan Fortea ; Kristian Steen Frederiksen ; Giovanni B Frisoni ab, Lutz Frölich ; Alejandro J. Garza-Martinez ; Timo Grimmer ; Bernard Hanseeuw ; Jakub Hort ag, Adrian Ivanoiu ; Patrick G Kehoe ; Sean P Kennelly ; Silke Kern ; Stefan Klöppel ; Lenka Krajčovičová ; Milica G. Kramberger ; Bernadette McGuinness ; Patrizia Mecocci ; Timo Jan Oberstein ; Pierre-Jean Ousset ; Claire Paquet ; Robert Perneczky ; Fabrizio Piazza ; Domenico Plantone ; Innocenzo Rainero ; Guillaume Sacco ; Eric Salmon ; Isabel Santana ; Nikolaos Scarmeas ; Anja Schneider ; Jonathan M Schott ; Eino Solje ; Elka Stefanova ; Elisabeth Stögmann ; Mélanie Strauss ; Stanislav Sutovsky ; Gunhild Waldemar ; Bengt Winblad (2025): Letter to the Editor: Comment by European Alzheimer’s Disease Consortium (EADC) investigators on the negative recommendation of the CHMP on the marketing authorization of donanemab for early Alzheimer’ s disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100259
LETTER TO THE EDITOR : REFINING THE EVIDENCE LINKING DIETARY DIVERSITY, GENETIC SUSCEPTIBILITY, AND DEMENTIA
Hongye Yao, Yangbo Lv
J Prev Alz Dis 2025;8(12)
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CITATION:
Hongye Yao ; Yangbo Lv (2025): Letter to the Editor : Refining the evidence linking dietary diversity, genetic susceptibility, and dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100247
REPLY TO LETTER TO THE EDITOR: “REFINING THE EVIDENCE LINKING DIETARY DIVERSITY, GENETIC SUSCEPTIBILITY, AND DEMENTIA”
Boyue Zhao, Boyue Zhao
J Prev Alz Dis 2025;8(12)
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CITATION:
Boyue Zhao ; Feng Zhang (2025): Reply to Letter to the Editor: “Refining the evidence linking dietary diversity, genetic susceptibility, and dementia”. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100246
LETTER TO THE EDITOR : THE SINGAPORE DEMENTIA PREVENTION PROGRAMME: TEN YEARS ON AND LOOKING AHEAD
Lei Feng, Kaisy Xinhong Ye, Lee Gan Goh, Ee-Heok Kua
J Prev Alz Dis 2025;8(12)
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CITATION:
Lei Feng ; Kaisy Xinhong Ye ; Lee Gan Goh ; Ee-Heok Kua (2025): Letter to the Editor : The singapore demen-tia prevention programme: Ten years on and looking ahead. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100272